Lab Notes: Parasites Hold IBD Clue

Parasitic worms are known to modulate the human host's intestinal immune response, in order to promote their survival in what would otherwise be a hostile environment. Now, some researchers think that worms can be used therapeutically for inflammatory bowel disease, and these researchers has also come up with a mechanistic explanation for this apparent benefit.

Writing in Science Translational Medicine, researchers at New York University and the University of California San Francisco describe a patient with ulcerative colitis who deliberately infected himself with the worm parasite Trichuris trichiura under their supervision.

His disease went into remission. The researchers noted that his intestinal mucosal cells were not producing IL-22 before the treatment but began churning out the cytokine when the worm infection took hold.

The findings suggest that treatments promoting IL-22 release -- perhaps with less of a "yuck" factor -- might also be effective in ulcerative colitis and other intestinal inflammatory disorders.

–J.G.

Protein Fights Fatty Effects

That Big Mac and fries might be fatal if it weren't for a particular protein in the gut, researchers found in a series of experiments. When saturated fat hits the intestinal lymphatic system, a protein known as Angptl4 is released to stop macrophages from breaking down the artery-clogging fat, "protecting against progressive, uncontrolled saturated fat-induced inflammation," they wrote in Cell Metabolism.

Mouse studies showed that without the protein, saturated fat intake led to a lethal immune reaction resulting in peritonitis, ascites, intestinal fibrosis, and wasting syndrome. The researchers speculated that in humans too, deficiencies in this protective pathway might be the source of inflammation linked to a diet high in saturated fat.

–C.P.

Air Pollution Increases Insulin Resistance in Mice

Exposure to air pollution resulted in the development of signs of insulin resistance in young mice.

A team led by researchers from Ohio State University fed two groups of mice a similar diet from age 3 weeks to 10 weeks. One group breathed air containing seven times the amount of fine particulates found in the ambient air for six hours a day, five days a week.

The exposure to pollution resulted in elevated levels of glucose and of the inflammatory biomarker tumor necrosis factor-alpha, as well as changes consistent with insulin resistance: enlarged subcutaneous and visceral fat contents, inflammation caused by increased macrophage infiltration in visceral adipose tissue, and vascular dysfunction.

"This is one of the first, if not the first study to show that these fine particulates directly cause inflammation and changes in fat cells, both of which increase the risk for type 2 diabetes," said lead author Qinghua Sun, MD, PhD, of Ohio State, in a statement.

The findings were reported in the December issue of Arteriosclerosis, Thrombosis, and Vascular Biology.

–T.N.

Rapid Prion Disease Assay

Researchers at the National Institute of Allergy and Infectious Diseases have developed an early, rapid test for diagnosing prion diseases such as mad cow and Creutzfeldt-Jakob disease.

Levels of prions in this fluid are usually too low to measure for diagnostic purposes, according to Byron Caughey, PhD, of NIAID's Rocky Mountain Laboratories in Hamilton, Mont. But the test can detect when even minuscule amounts of infectious prions begin converting large amounts of normal prions to abnormal forms.

After diluting the samples, scientists can observe which prions can still initiate conversion, according to the study in PLoS Pathogens. Thus they can estimate the relative infectious concentrations in the original samples.

The test could be useful for early diagnosis and treatment for these fatal diseases, although the researchers note that effective treatments are still in development.

–K.F.

Designing a Safer Steroid

Steroids -- the legal kind -- are among the most commonly used drugs worldwide, being prescribed for conditions ranging from asthma to cerebral edema and rheumatoid arthritis because of their potent anti-inflammatory and immunomodulatory actions.

However, when used for extended periods, these drugs are plagued by numerous serious adverse effects such as diabetes, osteoporosis, and hypertension.

Now, a group of scientists led by Rucha Patel of the University of Toronto have demonstrated that mice lacking a certain type of transcription factor known as liver X receptors (LXR)-beta are resistant to the detrimental metabolic effects of dexamethasone such as hyperglycemia and hepatic steatosis, yet remain sensitive to the therapeutic immunosuppressive effects.

In these mice, the researchers found "unexpected crosstalk" between LXR-beta and glucocorticoid receptors in the regulation of lipid and glucose metabolism.

Their findings "renew the optimism that a more selective [glucocorticoid] agonist can be designed to provide exceptional anti-inflammatory action without the development of negative metabolic effects," the researchers reported in the Journal of Clinical Investigation.

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